JP2015513544A5 - - Google Patents

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JP2015513544A5
JP2015513544A5 JP2014559183A JP2014559183A JP2015513544A5 JP 2015513544 A5 JP2015513544 A5 JP 2015513544A5 JP 2014559183 A JP2014559183 A JP 2014559183A JP 2014559183 A JP2014559183 A JP 2014559183A JP 2015513544 A5 JP2015513544 A5 JP 2015513544A5
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chem
glp
compound according
peptide
amide
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JP2015513544A (en
JP6300735B2 (en
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Priority claimed from PCT/EP2013/053796 external-priority patent/WO2013127779A1/en
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Claims (15)

一般式IのGLP-1化合物:
R1-(NHXaa1)-Xaa2-(OHis)-(GLP-1ペプチド)(式I)
[式中、
GLP-1ペプチドは、GLP-1(8-37)(配列番号1)、またはGLP-1(8-37)(配列番号1)と比較して最大で9個のアミノ酸の変化を有するその類似体であり、
R1は、低級アルキルであり、
(NHXaa1)は、アミノ酸であり、
Xaa2は、アミノ酸であり、
(OHis)は、式Chem.1
Chem.1:
Figure 2015513544
 のイミダゾール-乳酸のラジカルである]
またはその薬学的に許容される塩、アミド、もしくはエステル。 GLP-1 compounds of general formula I:
R1- (NHXaa1) -Xaa2- (OHis)-(GLP-1 peptide) (Formula I)
[Where
GLP-1 peptide has GLP-1 (8-37) (SEQ ID NO: 1), or its analog with up to 9 amino acid changes compared to GLP-1 (8-37) (SEQ ID NO: 1) Body,
R1 is lower alkyl,
(NHXaa1) is an amino acid,
Xaa2 is an amino acid,
(OHis) is the formula Chem.1
Chem. 1:
Figure 2015513544
 Is an imidazole-lactic acid radical]
Or a pharmaceutically acceptable salt, amide, or ester thereof. Xaa2と(OHis)との間の結合が、エステル結合である、請求項1に記載の化合物。   2. The compound according to claim 1, wherein the bond between Xaa2 and (OHis) is an ester bond. i)(NHXaa1)とXaa2との間、およびii)(OHis)と(GLP-1ペプチド)との間の結合が、アミド結合であり、R1が、(NHXaa1)のα-アミノ基に付着している、請求項1または2に記載の化合物。   The bond between i) (NHXaa1) and Xaa2, and ii) (OHis) and (GLP-1 peptide) is an amide bond, and R1 is attached to the α-amino group of (NHXaa1). The compound according to claim 1 or 2. R1が、メチルである、請求項1から3のいずれか一項に記載の化合物。   4. The compound according to any one of claims 1 to 3, wherein R1 is methyl. (NHXaa1)が、Gly、Val、またはIleである、請求項1から4のいずれか一項に記載の化合物。   The compound according to any one of claims 1 to 4, wherein (NHXaa1) is Gly, Val, or Ile. Xaa2が、Valである、請求項1から5のいずれか一項に記載の化合物。   6. The compound according to any one of claims 1 to 5, wherein Xaa2 is Val. GLP-1ペプチドが、少なくとも1つのアルブミン結合側鎖を含む誘導体である、請求項6に記載の化合物。   7. A compound according to claim 6, wherein the GLP-1 peptide is a derivative comprising at least one albumin binding side chain. GLP-1ペプチドが、
i)26位もしくは27位に付着した1つのアルブミン結合側鎖;または
ii)a)18位および31位のそれぞれ、b)26位および37位のそれぞれ、もしくはc)18位および26位のそれぞれに付着した1つのアルブミン結合側鎖
を有する誘導体であり、位置の付番は、GLP-1(8-37)(配列番号1)を意味する、請求項7に記載の化合物。 GLP-1 peptide
i) one albumin binding side chain attached at position 26 or 27; or
ii) Derivatives with one albumin binding side chain attached to a) positions 18 and 31, respectively, b) positions 26 and 37, or c) positions 18 and 26, respectively. The compound according to claim 7, wherein the number means GLP-1 (8-37) (SEQ ID NO: 1). Chem.51、Chem.52、Chem.53、Chem.54、Chem.55、およびChem.56から選択される化合物、またはその薬学的に許容される塩、アミドもしくはエステル：
Figure 2015513544
Figure 2015513544
Figure 2015513544
Figure 2015513544
Figure 2015513544
Figure 2015513544
 A compound selected from Chem. 51, Chem. 52, Chem. 53, Chem. 54, Chem. 55, and Chem. 56, or a pharmaceutically acceptable salt, amide or ester thereof:
Figure 2015513544
Figure 2015513544
Figure 2015513544
Figure 2015513544
Figure 2015513544
Figure 2015513544
 Chem.21、Chem.22、Chem.23、Chem.24、およびChem.25から選択される化合物、またはその薬学的に許容される塩、アミドもしくはエステル：
Figure 2015513544
Figure 2015513544
Figure 2015513544
Figure 2015513544
Figure 2015513544
 A compound selected from Chem. 21, Chem. 22, Chem. 23, Chem. 24, and Chem. 25, or a pharmaceutically acceptable salt, amide or ester thereof:
Figure 2015513544
Figure 2015513544
Figure 2015513544
Figure 2015513544
Figure 2015513544
 Chem.41、Chem.42、Chem.43、およびChem.44から選択される化合物、またはその塩、アミドもしくはエステル：
Figure 2015513544
 A compound selected from Chem. 41, Chem. 42, Chem. 43, and Chem. 44, or a salt, amide or ester thereof:
Figure 2015513544
 医薬として使用するための、請求項1から10のいずれか一項に記載の化合物。   11. A compound according to any one of claims 1 to 10 for use as a medicament. 摂食障害、心血管疾患、胃腸疾患、糖尿病性合併症、重篤疾患、および/もしくは多嚢胞性卵巣症候群から成る群から選択される全ての形態の糖尿病および関連する疾患の治療および/もしくは予防において使用するため;ならびに/または脂質パラメーターを改善するため、β-細胞機能を改善するため、ならびに/または糖尿病性疾患の進行を遅延もしくは予防するための、請求項1から10のいずれか一項に記載の化合物。 Eating disorders, cardiovascular disease, gastrointestinal diseases, diabetic complications, severe diseases, and / or the treatment and / or prevention of polycystic all forms of diabetes and related disease selected from the group consisting of ovary syndrome And / or for improving lipid parameters, for improving β-cell function, and / or for delaying or preventing the progression of diabetic disease. Compound described in 1. 摂食障害、心血管疾患、胃腸疾患、糖尿病性合併症、重篤疾患、および多嚢胞性卵巣症候群から成る群から選択される全ての形態の糖尿病および関連する疾患を治療もしくは予防するため;ならびに/または脂質パラメーターを改善するため、β-細胞機能を改善するため、ならびに/または糖尿病性疾患の進行を遅延もしくは予防するための、請求項1から10のいずれか一項に記載の化合物を含む医薬組成物。 Eating disorders, cardiovascular disease, gastrointestinal diseases, diabetic complications, severe diseases, and all forms of diabetes and related diseases for the treatment or prophylaxis is selected from the group consisting of polycystic ovarian syndrome 11. and / or a compound according to any one of claims 1 to 10 for improving lipid parameters, for improving β-cell function, and / or for delaying or preventing the progression of diabetic disease . A pharmaceutical composition comprising 一般式II:(HOHis)-(GLP-1ペプチド)の活性であり安定化した親薬物GLP-1化合物、またはその薬学的に許容される塩、アミド、もしくはエステルのインビボでの放出を達成するための、請求項1から9のいずれか一項に規定するそのプロドラッグを含む医薬組成物。 One general formula II: (HOHis) - achieving release of the active and is the parent drug GLP-1 compound was stabilized, or a pharmaceutically acceptable salt, amide or in vivo of the ester, the (GLP-1 peptide) A pharmaceutical composition comprising a prodrug thereof as defined in any one of claims 1 to 9 for doing so .
JP2014559183A 2012-03-01 2013-02-26 GLP-1 prodrug Active JP6300735B2 (en)

Applications Claiming Priority (3)

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EP12157638.3 2012-03-01
EP12157638 2012-03-01
PCT/EP2013/053796 WO2013127779A1 (en) 2012-03-01 2013-02-26 Glp-1 prodrugs

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JP2015513544A5 true JP2015513544A5 (en) 2016-03-03
JP6300735B2 JP6300735B2 (en) 2018-03-28

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CN (1) CN104185639B (en)
ES (1) ES2810153T3 (en)
WO (1) WO2013127779A1 (en)

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PL3870213T3 (en) * 2018-10-26 2023-11-20 Novo Nordisk A/S Stable semaglutide compositions and uses thereof
EP4106724A1 (en) 2020-02-18 2022-12-28 Novo Nordisk A/S Glp-1 compositions and uses thereof
CN113336840B (en) * 2020-03-02 2022-09-23 武汉帕肽生物医药有限责任公司 Stapled peptides, methods of making and uses thereof
PE20240630A1 (en) 2020-11-06 2024-03-26 Novo Nordisk As GLP-1 PRODRUGS AND USES THEREOF
WO2023217744A1 (en) 2022-05-10 2023-11-16 Novo Nordisk A/S Prodrugs of glp-1 polypeptide and uses thereof

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